Family based association study of DRD1, DRD2, DRD3, DRD4, DAT, COMT gene polymorphism in schizophrenia
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Psychiatr Pol 2010;44(3):405–413
Aim. The aim of the study was to estimate of the transmission of six candidate genes alleles (according to the dopaminergic hypothesis of schizophrenia) by parents to their children with schizophrenia. The genes under investigation were the following: DRD1 (polymorphism -48A/G), DRD2 (polymorphism -14IC ins/del), DRD3 (polymorphism Ser9Gly), DRD4 (polymorphism -521C/T), DAT (polymorphism VNTR w 3'-UTR), COMT (polymorphism Val108(158)Met). Method. There were 116 families in the group under investigation (the ill person and his/her both parents). The patients and their parents were examined using SCID (Structured Clinical Interview for DSM-IV Axis I Disorders). No mental disturbances were found with all the patients' parents. The DNA was extracted from the peripheral blood leukocytes by the salting out method. Polymorphisms were studied by the PCR method (PCR-RFLP method for: DRD1, DRD2, DRD3, DRD4, COMT and PCR-VNTR method for: DAT). The statistical analysis of the frequency of transmission of alleles was carried out by the TDT (Transmission Disequilibrium Test) method. To analyse the transmission disequilibrium of alleles under examination, the Haploview v. 3.2. programme was used. Results. According to the results obtained, no connection between analysed polymorphism of genes: DRD2 (-141C ins/del), DRD3 (Ser9Gly), DRD4 (-521C/T), DAT (VNTR), COMT (Val108(158)Met) and schizophrenia was stated. In the case of polymorphism -48A/G of gene DRD1, a trend was observed towards a more frequent transmission of allele A of gene DRD1 by parents to their children with schizophrenia (p=0.091). Conclusions. This trend should be interpreted very carefully. There is also the possibility that other variant of gene in linkage disequilibrium with -48A/G polymorphism was responsible for the trend observed in this study.